The effect of heparin-functionalized PEG hydrogels on three-dimensional human mesenchymal stem cell osteogenic differentiation

Benoit, Danielle S. W.; Durney, Andrew R.; Anseth, Kristi S.

doi:10.1016/j.biomaterials.2006.08.033

Cited by 223 publications

(195 citation statements)

References 39 publications

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“…It is most probable that this elongated morphology causes cellular cytoskeletal tension and stress on the hMSCs cultured on 70-to 100-nm diameter regime nanotubes compared with a normal cell culture condition on a flat surface substrate. It is well known that various kinds of physical stresses from the substrate morphology and topography can accelerate stem cell differentiation into a specific cell lineage (29)(30)(31)(32)(33)(34)(35); our data show a similar scenario.…”

Section: Discussionsupporting

confidence: 77%

Stem cell fate dictated solely by altered nanotube dimension

Oh¹,

Brammer²,

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

1,103

914

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Two important goals in stem cell research are to control the cell proliferation without differentiation and to direct the differentiation into a specific cell lineage when desired. Here, we demonstrate such paths by controlling only the nanotopography of culture substrates. Altering the dimensions of nanotubular-shaped titanium oxide surface structures independently allowed either augmented human mesenchymal stem cell (hMSC) adhesion or a specific differentiation of hMSCs into osteoblasts by using only the geometric cues, absent of osteogenic inducing media. hMSC behavior in response to defined nanotube sizes revealed a very dramatic change in hMSC behavior in a relatively narrow range of nanotube dimensions. Small (Ϸ30-nm diameter) nanotubes promoted adhesion without noticeable differentiation, whereas larger (Ϸ70-to 100-nm diameter) nanotubes elicited a dramatic stem cell elongation (Ϸ10-fold increased), which induced cytoskeletal stress and selective differentiation into osteoblast-like cells, offering a promising nanotechnology-based route for unique orthopedics-related hMSC treatments.differentiation ͉ mesenchymal ͉ nanotopography ͉ osteogenesis ͉ proliferation N anostructures are of particular interest because they have the advantageous feature of a high surface-to-volume ratio, and they elicit a higher degree of biological plasticity compared with conventional micro-or macrostructures. In the field of biomaterial development and in vivo implant technology, the nanoscale structure and morphologenic factor of the surface have played a critical role in accelerating the rate of cell proliferation and enhancing tissue acceptance with a reduced immune response (1, 2). In terms of in vitro cell biology, there has also been much attention placed on cellular responses to their structural surroundings (3). In fact, it has been observed that macro-, micro-and nano-sized topographical factors stimulate behavioral changes in both cells and tissues. Recent studies related to the effect of nanotopography on cellular behavior indicated that osteoblast adhesion and functionality was enhanced by 30% when cultured on a nanograined Al 2 O 3 and TiO 2 substrate (4-6) compared with those cultured on a micrograined surface, and nanostructures such as TiO 2 nanotubes with Ͻ100-nm spacing showed superior characteristics in bone mineral synthesis (5). However, most of the previous studies on nanostructures and cell responses have mainly used oriented, patterned, or semiordered polymer arrays (7-9) and alumina/ polymer hybrid patterned arrays (10).The material and mechanical characteristics of titanium (Ti) metal, which has a thin native oxide layer of TiO 2 , make it an ideal orthopedic material that bonds directly to the adjacent bone surface (11,12). Fabrication of the nanostructured titanium dioxide (TiO 2 ) nanotube arrays has been a primary subject of investigation lately because of the wide range of TiO 2 applications in the fields of solar cells (13-16), photocatalysis (17-19), photoelectrolysis (20), sensors (21,22), and b...

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Section: Discussionsupporting

confidence: 77%

Stem cell fate dictated solely by altered nanotube dimension

Oh¹,

Brammer²,

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

1,103

914

View full text Add to dashboard Cite

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“…S3), consistent with PEG hydrogel literature. 41,52,[61][62][63][64] Following 7 days of culture, a variety of chondrocytic anabolic, catabolic, and inflammatory markers were analyzed by qRT-PCR, western blot, multiplex protein assays, and/or immunostaining. Representative western blot and immunostaining images are shown in Supplementary Figures S4-S6.…”

Section: D System To Study Effects Of Osteoarthritic Inflammationmentioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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“…19,20 MSCs can differentiate into different cells with ectodermal and endodermal characteristics, suggesting the possibility of MSCs for cell replacement and tissue regeneration. [21][22][23][24][25] The previous MSC research has focused on the effects of soluble cues, such as growth factors and cytokines. 26 However, there are increasing interests on understanding how extracellular matrix (ECM) components influence MSC behaviour and properties.…”

Section: Introductionmentioning

confidence: 99%

Covalently immobilized biomolecule gradient on hydrogel surface using a gradient generating microfluidic device for a quantitative mesenchymal stem cell study

Liu

Liang

et al. 2012

Biomicrofluidics

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Precisely controlling the spatial distribution of biomolecules on biomaterial surface is important for directing cellular activities in the controlled cell microenvironment. This paper describes a polydimethylsiloxane (PDMS) gradient-generating microfluidic device to immobilize the gradient of cellular adhesive Arg-Gly-Asp (RGD) peptide on poly (ethylene glycol) (PEG) hydrogel. Hydrogels are formed by exposing the mixture of PEG diacrylate (PEGDA), acryloyl-PEG-RGD, and photo-initiator with ultraviolet light. The microfluidic chip was simulated by a fluid dynamic model for the biomolecule diffusion process and gradient generation. PEG hydrogel covalently immobilized with RGD peptide gradient was fabricated in this microfluidic device by photo-polymerization. Bone marrow derived rat mesenchymal stem cells (MSCs) were then cultured on the surface of RGD gradient PEG hydrogel. Cell adhesion of rat MSCs on PEG hydrogel with various RGD gradients were then qualitatively and quantitatively analyzed by immunostaining method. MSCs cultured on PEG hydrogel surface with RGD gradient showed a grated fashion for cell adhesion and spreading that was proportional to RGD concentration. It was also found that 0.107-0.143 mM was the critical RGD concentration range for MSCs maximum adhesion on PEG hydrogel.

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The effect of heparin-functionalized PEG hydrogels on three-dimensional human mesenchymal stem cell osteogenic differentiation

Cited by 223 publications

References 39 publications

Stem cell fate dictated solely by altered nanotube dimension

Stem cell fate dictated solely by altered nanotube dimension

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Covalently immobilized biomolecule gradient on hydrogel surface using a gradient generating microfluidic device for a quantitative mesenchymal stem cell study

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